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Friday, May 31, 2013

Vaccines, Autism, and the Scientific Method

Disclaimer:As with other articles posted in this blog, several of the links will lead you to the original research articles as they are found on the websites of their respective publishers. I feel it is important to provide citations that direct people to the purest source of information that is available. Unfortunately, many journal publishers cannot allow free access to the public of full articles, so the links may allow you to see only the abstracts in some cases. Full articles can be purchased, or accessed via university networks that have a paid subscription with publishers.

Prologue

It is a well-known axiom in any science that ‘correlation
does not imply causation’. Because
coincidences run rampant in nature and in life, focused efforts must be made to
extract the effect with its true cause from a mess of random concurrences. This is where the scientific method comes in (Figure 1). The observation of simultaneous events may
lead one to hypothesize that one causes the other. But, before any solid conclusions can be
drawn there is a prerequisite step: Experimentation. This is the inconvenient step; the one that
requires meticulous planning, long drawn-out trials, repetition, peer-review of
the results, and funding. This step was bypassed
by some during the early 2000’s in their zeal to hop to the conclusion that
vaccines cause autism. But 13 years later,
some new results are in from a very broad study designed to probe the alleged
vaccine/autism link.

Figure 1. The fundamental scientific method, shown left. The box on the right shows how faulty theories can be drawn from conclusions that have no experimental basis and incidentally no results to support them.

Observation

First, we go back to 1998 when the correlation was most
ostensibly observed. Andrew Wakefield
was at the time a doctor and medical researcher specializing in bowel disorders
at the London Royal Free Hospital School of Medicine. In the prestigious medical journal The Lancet, Wakefield was the lead
author of a published
observation that 12 children (11 boys, 1 girl; ages 3 - 10) were all diagnosed with
autism-related behavior abnormalities by parents or physicians after receiving
the measles-mumps-rubella (MMR) vaccine.
It was noted that 8 of these children had a confirmed onset of
behavioral abnormalities within 1-14 days following vaccination. All 12 children also were found to possess
gastrointestinal disorders. Wakefield’s
work was funded by the UK Special Trustees of Royal Free Hampstead NHS Trust
and the Children's Medical Charity.

Hypothesis

In consideration of the fact that rates of autism were on
the rise (and continue
to be) following the introduction of the MMR vaccine in 1988 in the UK, a
hypothesis appeared to become self-evident.
As stated objectively in Wakefield’s paper:

“We identified associated gastrointestinal disease and
developmental regression in a group of previously normal children, which was
generally associated in time with possible environmental triggers.”

The ‘environmental triggers’ referred to here is the MMR
vaccine. So, to paraphrase the
hypothesis: ‘12 kids that were once normal now have bowel problems and autism,
and we think these issues might be correlated, and there is a possibility that both
could be caused by the MMR vaccine’. This
was a fair observation worthy of further investigation, based on the data
presented. The authors conservatively
added:

“We did not prove an association between measles, mumps,
and rubella vaccine and the syndrome described. Virological studies are
underway that may help to resolve this issue.”

This caution was appropriate considering that the sample
size was small (12 cases) and the study involved no controls (children not
exposed to the vaccine, or children not diagnosed with autism) for
comparison. Because the diagnosis of
autism usually happens early in life, as do vaccinations, controls would be
indispensable for proving a casue/effect relationship. Otherwise one could just as well declare that
Flinstones Vitamins are the cause of autism and/or gastrointestinal irregularities.

Retraction

The publication of Wakefield’s paper caused a stir as
people mulled the impossible choice between protecting their children from
infectious diseases, or protecting them from autism. Inevitably, a few chose to abstain from vaccinating
their children. A few years later, an
increase in measles cases began to emerge in the UK. In light of this, 10 of the 12 authors on
Wakefield’s 1998 paper clarified their position by issuing a formal ‘Retractionof an Interpretation’ in a 2004 publication of The Lancet:

“The main thrust of this paperwas the first
description of an unexpected intestinal lesion in the children reported….We wish
to make it clear that in this paper no causal link was established between MMR
vaccine and autism as the data were insufficient.”

While these 10 authors attempted to distance themselves
from a proposed hypothesis that was mistaken for a conclusion among a small
segment of the general public, one author was conspicuously absent from this
statement: Andrew Wakefield. The journal
responded
in the same issue by reporting that an investigation was carried out and
focused on the methods used in the 1998 study and found no ethical violations. However, six years later, not only was this
statement of support retracted by The
Lancet, but the entire 1998 paper was retracted:

“Following the judgment of the UK General Medical
Council's Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al are incorrect, contrary to the findings of an earlier investigation. In particular, the claims in the original paper that children were "consecutively referred" and that investigations were "approved" by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record."

Statements
by the editors in the media were far less diplomatic than this carefully worded
retraction. Serious aspersions were cast
by journalists and others in the
scientific community. Conversely, a few publicly
defended
Wakefield amidst the kerfuffle that ensued. Andrew Wakefiled lost his medical licence, but responded by telling his
side of the story in a 2010 book,
and continues to stand firmly by his original hypothesis.

By 2011, the World Health Organizahtion (WHO) sternly urged
Europeans to vaccinate their children in response to 26,000 recorded cases of
the once rare measles. 90% of those
cases had not received the vaccine. The
Centers for Disease Control (CDC) issued similar warnings in response to much
smaller outbreaks that
followed in the U.S., where the disease was previously considered to be
practically eradicated. Clusters
were observed in highly populated cities, as well as in Minnesota
and Utah.

Experimentation

Going back now to 2000, an elaborate study designed to investigate
vaccines as a cause for autism was initiated in by Frank DeStefano and
colleagues at the US Centers for Disease Control (CDC), which funded the study. This study involved a much larger sample size
as well as controls: 256 children on the autism spectrum, and 752 without
autism were included in the study. All
children received some level of vaccination.
The control subjects were matched for comparison to autistic subjects
according to the child’s age, gender, and managed care provider. The children were 85% male. Data on these children were compiled retroactively
from the records of three separate managed health care providers. This data included the types and amount of
vaccines each child received, when they received them, and when they were
professionally diagnosed with autism. Data
for 24 separate vaccines were included in the study, including MMR. At the time, many of these vaccines contained
thimerosal
as a preservative – a compound that has caused concerns due to its mercury
content. The care providers examined the
children for autism during the vaccination period at the points of 3 months, 7
months, and 24 months. Comparisons were
made among children with and without autism, and how much of which vaccines
they received, when they received them, and when the onset of autism symptoms
began.

Results and Conclusions

The data was meticulously combed through over the
course of the following years, and correlations were probed. The results were published
in an April 2013 issue of the Journal of
Pediatrics, with charts and graphs
showing that an increase in exposure to vaccine immunogens does not correlate
to an increase in autism diagnosis.
Accordingly, the following succinct conclusion was stated:

“We found no evidence indicating an association between
exposure to antibody-stimulating proteins and polysaccharides contained in
vaccines during the first 2 years of life and the risk of acquiring ASD, AD, or
ASD with regression.”

This conclusion is corroborated by several
earlier studies that have been published elsewhere in the scientific
literature.

Epilogue

Uncertainty is a sentiment that any disciplined scientist
must learn to be comfortable with. It is
the gap between questions and answers that compels research to keep moving
forward. Autism is a question that
deserves answers, and it would be comforting to believe with certainty that we
have found them. However, this does not
yet appear to be the case. Because the
works of science are often communicated in a language that many don’t speak,
people often must accept or reject them as an act of faith. It is my intention and hope that such faith
in scientific methods can be perfected by making
the works more accessible. In writing
this post, my bias was obviously in favor of the work that I am familiar with
that was presented here. But all
conclusions are subject to dialogue. If
you are aware of peer-reviewed reliable scientific research that does
demonstrate a cause/effect relationship of vaccines and autism, by all means
post it in the comments. Thank you!